International Journal for Parasitology: Drugs and Drug Resistance最新文献

{"title":"Deep-amplicon sequencing of the complete beta-tubulin gene in Trichuris trichiura before and after albendazole treatment","authors":"Javier Gandasegui ,&nbsp;Berta Grau-Pujol ,&nbsp;Valdemiro Novela ,&nbsp;Osvaldo Muchisse ,&nbsp;Maria Cambra-Pellejà ,&nbsp;Anélsio Cossa ,&nbsp;José Carlos Jamine ,&nbsp;Charfudin Sacoor ,&nbsp;Eric A.T. Brienen ,&nbsp;Francesc Catala-Moll ,&nbsp;Lisette van Lieshout ,&nbsp;María Martínez-Valladares ,&nbsp;Roger Paredes ,&nbsp;José Muñoz ,&nbsp;Stephen R. Doyle","doi":"10.1016/j.ijpddr.2024.100570","DOIUrl":"10.1016/j.ijpddr.2024.100570","url":null,"abstract":"<div><div>Concerns about the emergence of benzimidazole resistance in soil-transmitted helminths (STH) infections, particularly against <em>Trichuris trichiura</em>, have arisen. Previous studies of veterinary nematodes have linked benzimidazole resistance to single-nucleotide polymorphisms (SNPs) at three specific codons in the beta-tubulin gene, but similar associations in STH have not been consistently observed. In this work, we screened the complete beta-tubulin gene previously linked to benzimidazole resistance in <em>T. trichiura</em> by deep-amplicon sequencing to identify genetic variants and associate levels of diversity with drug response to albendazole. We used 99 DNA samples extracted from <em>T. trichiura</em> pooled eggs, previously semi-purified from human stool samples collected in Manhiça district, Mozambique. We obtained a set of 39 amplicons of the complete gene by subjecting the pooled eggs to long-read PCR and subsequently sequencing them. Of those amplicons, 22 and 17 were obtained from stool samples collected before, and 21 days after albendazole treatment, respectively. We observed genetic variation across the whole gene sequence, in both exons and introns; however, none were associated with the previously proposed resistance-associated SNPs, and none were predicted to significantly affect protein function. No significant differences in genetic diversity were observed between pre- and post-treatment samples. Using publicly available genome-wide data, we also analysed a second beta-tubulin isotype in the <em>T. trichiura</em> genome. We focused on detecting the canonical SNPs and assessing for signatures of genetic selection around this second isotype gene. This analysis did not reveal evidence supporting this second isotype's role in anthelmintic resistance. Despite the limitations of our study, such as a small sample size, particularly paired pre- and post-treatment samples (n = 6), or a restricted geographical area, we found no evidence linking either of the two beta-tubulin genes to benzimidazole resistance in <em>T. trichiura</em>, suggesting that genetic markers of drug resistance likely exist outside the beta-tubulin genes.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100570"},"PeriodicalIF":4.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid detection of mutations in the suspected piperaquine resistance gene E415G-exo in Plasmodium falciparum exonuclease via AS‒PCR and RAA with CRISPR/Cas12a","authors":"Huiyin Zhu ,&nbsp;Daiqian Zhu ,&nbsp;Yuting Li ,&nbsp;Yun Li ,&nbsp;Xiaonan Song ,&nbsp;Jinyu Mo ,&nbsp;Long Liu ,&nbsp;Zhixin Liu ,&nbsp;Siqi Wang ,&nbsp;Yi Yao ,&nbsp;He Yan ,&nbsp;Kai Wu ,&nbsp;Wei Wang ,&nbsp;Jianhai Yin ,&nbsp;Min Lin ,&nbsp;Jian Li","doi":"10.1016/j.ijpddr.2024.100568","DOIUrl":"10.1016/j.ijpddr.2024.100568","url":null,"abstract":"<div><div>Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS<strong>‒</strong>PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the <em>Plasmodium falciparum exonuclease</em> (<em>Pfexo</em>) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS<strong>‒</strong>PCR, and crRNA-mismatched bases were introduced into the RAA<strong>‒</strong>CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS<strong>‒</strong>PCR and RAA<strong>‒</strong>CRISPR/Cas12a assays were 10⁴ copies/μL and 10³ copies/μL, respectively. The detection threshold for dried blood spots was 100<strong>‒</strong>150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS<strong>‒</strong>PCR is approximately $1 per test and takes 2<strong>–</strong>3 h, whereas that of the RAA<strong>‒</strong>CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the <em>Pfexo</em> gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100568"},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profile of molecular markers of Sulfadoxine-Pyrimethamine-resistant Plasmodium falciparum in individuals living in southern area of Brazzaville, Republic of Congo","authors":"Jean Claude Djontu ,&nbsp;Marcel Tapsou Baina ,&nbsp;Jacque Dollon Mbama Ntabi ,&nbsp;Abel Lissom ,&nbsp;Dieu Merci Umuhoza ,&nbsp;Naura veil Assioro Doulamo ,&nbsp;Christevy Jeanney Vouvoungui ,&nbsp;Reauchelvy Kamal Boumpoutou ,&nbsp;Alain Maxime Mouanga ,&nbsp;Etienne Nguimbi ,&nbsp;Francine Ntoumi","doi":"10.1016/j.ijpddr.2024.100569","DOIUrl":"10.1016/j.ijpddr.2024.100569","url":null,"abstract":"<div><h3>Background</h3><div>Although the seasonal and perennial malaria chemopreventions are not implemented in the Republic of Congo, resistance to Sulfadoxine-pyrimethamine (SP) threatens the intermittent preventive treatment during pregnancy (IPTp-SP) and others treatments using the drug. The objective of this study was to determine the prevalence of molecular markers of <em>P.falciparum</em> resistance to SP in individuals with microscopic malaria infection in the south of Brazzaville.</div></div><div><h3>Methods</h3><div>Two parallel surveys (health facilities and community-based cross sectional studies) were carried out in urban and rural areas in southern Brazzaville. Between March and October 2021, blood samples were collected from 328 <em>P. falciparum</em> microscopic positive individuals (1–83 years old, and sex ratio female/male of 1.1) to characterize <em>dhfr</em> and <em>dhps</em> genes involved in the <em>P.falciparum</em> resistance to SP. Restriction Fragment Length Polymorphism PCR was used for the detection of mutations within these parasite genes.</div></div><div><h3>Results</h3><div>High prevalence of mutations was reported within <em>Pfdhfr</em> gene: N51<strong>I</strong>; 328/328 (100%) ratio (prevalence) [95 CI uncertainty], C59<strong>R</strong>; 317/328 (96.6 %) [94.1–98.1%], S108<strong>N;</strong> 326/326 (100%), N164<strong>L;</strong> 3/326 (0.9%) [0.3–2.7%], and <em>Pfdhps</em> gene: A437<strong>G</strong>; 292/327 (89.3%) [85.5–92.2%], K540<strong>E</strong>; 140/327(42.8 %) [37.6–48.2%], A581<strong>G</strong>; 136/325 (41.8%) [36.6–42.3%]. The quintuple mutant (N51<strong>I</strong> + C59<strong>R</strong> + S108<strong>N +</strong> A437<strong>G</strong> + K540<strong>E)</strong> and sextuple mutant haplotypes (N51<strong>I</strong> + C59<strong>R</strong> + S108<strong>N +</strong> A437<strong>G</strong> + K540<strong>E +</strong> A581<strong>G)</strong> were reported for 11/144 (7.6%) [4.3–13.2%] and 5/144 (3.4%) [1.5–7.9%]) of the participants respectively. The K540<strong>E</strong> and A437<strong>G</strong> mutants were more prevalent in the rural community; 81/139 (58.3%) [50.0–66.1%] and 135/139 (97.1%) [92.8–98.9%] respectively) than in the urban community; 21/50 (46.3%) [33.7–59.4%] and 47/54(87.0%) [75.6–93.6%] (p = 0.004 and p˂0.0001 respectively)</div></div><div><h3>Conclusion</h3><div>These results indicate high prevalence of SP resistance mutations within the <em>dhfr</em> and <em>dhps</em> genes of <em>P. falciparum</em> isolates circulating in study sites, which may limit the efficacy of treatments using SP in these settings.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100569"},"PeriodicalIF":4.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast-based assay to identify inhibitors of the malaria parasite sodium phosphate uptake transporter as potential novel antimalarial drugs","authors":"Joseph M. Sweeney ,&nbsp;Ian M. Willis ,&nbsp;Myles H. Akabas","doi":"10.1016/j.ijpddr.2024.100567","DOIUrl":"10.1016/j.ijpddr.2024.100567","url":null,"abstract":"<div><div>Malaria affects almost 250 million people annually and continues to be a significant threat to global public health. Infection with protozoan parasites from the genus <em>Plasmodium</em> causes malaria. The primary treatment for malaria is artemisinin-based combination therapies (ACTs). The spread of ACT-resistant parasites has undermined efforts to control and eradicate malaria. Thus, it is crucial to identify new targets for the development of novel antimalarial drugs. Phosphate is an essential nutrient for all cells. The <em>Plasmodium falciparum</em> genome encodes a single sodium-coupled inorganic phosphate transporter named PfPiT that is essential for parasite proliferation in the asexual blood stage. Thus, PfPiT inhibitors may be promising antimalarial drugs. Like <em>Plasmodium</em>, yeast requires phosphate to grow. We developed a <em>Saccharomyces cerevisiae</em> based growth assay to identify inhibitors of PfPiT. Genome editing was used to create a yeast strain where PfPiT was the only phosphate transporter. Using a radioactive [³²P]phosphate uptake assay, the measured phosphate K_m for PfPiT in yeast was 56 ± 7 μM in 1 mM NaCl at pH 7.4. The K_m decreased to 24 ± 3 μM in 25 mM NaCl consistent with it being a Na⁺ coupled cotransporter. Conditions under which yeast growth was dependent on phosphate uptake mediated by PfPiT were identified and a 22-h growth assay was developed to screen for PfPiT inhibitors. In a screen of 21 compounds, two compounds were identified that inhibited the growth of the PfPiT strain but not that of the parental strain expressing Pho84, one of the five endogenous yeast phosphate transporters. Radioactive phosphate uptake experiments confirmed inhibition of phosphate uptake by the two compounds. The growth inhibition assay provides a simple and inexpensive approach to screen a large compound library for PfPiT inhibitors that may serve as starting points for the development of novel antimalarial drugs.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100567"},"PeriodicalIF":4.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative proteomic analysis of metronidazole-sensitive and resistant Trichomonas vaginalis suggests a novel mode of metronidazole action and resistance","authors":"Anna-Lena Mayr ,&nbsp;Ana Paunkov ,&nbsp;Karin Hummel ,&nbsp;Ebrahim Razzazi-Fazeli ,&nbsp;David Leitsch","doi":"10.1016/j.ijpddr.2024.100566","DOIUrl":"10.1016/j.ijpddr.2024.100566","url":null,"abstract":"<div><div>The microaerophilic parasite <em>Trichomonas vaginalis</em> occurs worldwide and causes inflammation of the urogenital tract, especially in women. With 156 million infections annually, trichomoniasis is the most prevalent non-viral sexually transmitted disease. Trichomoniasis is treated with 5-nitroimidazoles, especially metronidazole, which are prodrugs that have to be reduced at their nitro group to be activated. Resistance rates to metronidazole have remained comparably low, but they can be higher in certain areas leading to an increase of refractory cases. Metronidazole resistance in <em>T</em>. <em>vaginalis</em> can develop <em>in vivo</em> in clinical isolates, or it can be induced in the laboratory. Both types of resistance share certain characteristics but differ with regard to the dependence of ambient oxygen to become manifest. Although several candidate factors for metronidazole resistance have been described in the past, e.g. pyruvate:ferredoxin oxidoreductase and ferredoxin or thioredoxin reductase, open questions regarding their role in resistance have remained.</div><div>In order to address these questions, we performed a proteomic study with metronidazole-sensitive and –resistant laboratory strains, as well as with clinical strains, in order to identify factors causative for resistance. The list of proteins consistently associated with resistance was surprisingly short. Resistant laboratory and clinical strains only shared the downregulation of flavin reductase 1 (FR1), an enzyme previously identified to be involved in resistance. Originally, FR1 was believed to be an oxygen scavenging enzyme, but here we identified it as a ferric iron reductase which produces ferrous iron. Based on this finding and on further experimental evidence as presented herein, we propose a novel mechanism of metronidazole activation which is based on ferrous iron binding to proteins, thereby rendering them susceptible to complex formation with metronidazole. Upon resolution of iron-protein-metronidazole complexes, metronidazole radicals are formed which quickly react with thiols or proteins in the direct vicinity, leading to breaks in the peptide backbone.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100566"},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In artemisinin-resistant falciparum malaria parasites, mitochondrial metabolic pathways are essential for survival but not those of apicoplast","authors":"Manel Ouji ,&nbsp;Thibaud Reyser ,&nbsp;Yoshiki Yamaryo-Botté ,&nbsp;Michel Nguyen ,&nbsp;David Rengel ,&nbsp;Axelle Dutreuil ,&nbsp;Marlène Marcellin ,&nbsp;Odile Burlet-Schiltz ,&nbsp;Jean-Michel Augereau ,&nbsp;Michael K. Riscoe ,&nbsp;Lucie Paloque ,&nbsp;Cyrille Botté ,&nbsp;Françoise Benoit-Vical","doi":"10.1016/j.ijpddr.2024.100565","DOIUrl":"10.1016/j.ijpddr.2024.100565","url":null,"abstract":"<div><div>Emergence and spread of parasite resistance to artemisinins, the first-line antimalarial therapy, threaten the malaria eradication policy. To identify therapeutic targets to eliminate artemisinin-resistant parasites, the functioning of the apicoplast and the mitochondrion was studied, focusing on the fatty acid synthesis type II (FASII) pathway in the apicoplast and the electron transfer chain in the mitochondrion. A significant enrichment of the FASII pathway among the up-regulated genes in artemisinin-resistant parasites under dihydroartemisinin treatment was found, in agreement with published transcriptomic data. However, using GC-MS analyzes of fatty acids, we demonstrated for the first time that the FASII pathway is non-functional, ruling out the use of FASII inhibitors to target artemisinin-resistant parasites. Conversely, by assessing the modulation of the oxygen consumption rate, we evidenced that mitochondrial respiration remains functional and flexible in artemisinin-resistant parasites and even at the quiescent stage. Two novel compounds targeting electron transport chain (ELQ300, ELQ400) efficiently killed quiescent artemisinin-resistant parasites. Therefore, mitochondrial respiration represents a key target for the elimination of artemisinin-resistant persistent <em>Plasmodium falciparum</em> parasites.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100565"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the amoeba thioredoxin reductase selenoprotein as potential drug target for treatment of Acanthamoeba infections","authors":"Alvie Loufouma-Mbouaka ,&nbsp;Attila Andor ,&nbsp;David Leitsch ,&nbsp;Jorge Pérez-Serrano ,&nbsp;Elias S.J. Arnér ,&nbsp;Julia Walochnik ,&nbsp;Tania Martín-Pérez","doi":"10.1016/j.ijpddr.2024.100564","DOIUrl":"10.1016/j.ijpddr.2024.100564","url":null,"abstract":"<div><div>The genus <em>Acanthamoeba</em> comprises facultative pathogens, causing <em>Acanthamoeba</em> keratitis (AK) and granulomatous amoebic encephalitis (GAE). In both diseases, treatment options are limited, and drug development is challenging. This study aimed to investigate the role of the large thioredoxin reductase selenoprotein of <em>Acanthamoeba</em> (AcTrxR-L) as a potential drug target assessing the effects of the thioredoxin reductase inhibitors auranofin, TRi-1, and TRi-2 on AcTrxR-L activity and on the viability of <em>Acanthamoeba</em> trophozoites. Recombinant expression and purification of AcTrxR-L as a selenoprotein allowed assessments of its enzymatic activity, with reduction of various substrates, including different thioredoxin isoforms. Auranofin demonstrated potent inhibition towards AcTrxR-L, followed by TRi-1, and TRi-2 exhibiting lower effectiveness. The inhibitors showed variable activity against trophozoites in culture, with TRi-1 and TRi-2 resulting in strongly impaired trophozoite viability. Cytotoxicity tests with human corneal epithelial cells revealed lower susceptibility to all compounds compared to <em>Acanthamoeba</em> trophozoites, underscoring their potential as future amoebicidal agents. Altogether, this study highlights the druggability of AcTrxR-L and suggests it to be a promising drug target for the treatment of <em>Acanthamoeba</em> infections. Further research is warranted to elucidate the role of AcTrxR-L in <em>Acanthamoeba</em> pathogenesis and to develop effective therapeutic strategies targeting this redox enzyme.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100564"},"PeriodicalIF":4.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The phosphatase inhibitor BVT-948 can be used to efficiently screen functional sexual development proteins in the malaria parasite Plasmodium berghei","authors":"Xitong Jia ,&nbsp;Yong Wang ,&nbsp;Meilian Wang ,&nbsp;Hui Min ,&nbsp;Zehou Fang ,&nbsp;Haifeng Lu ,&nbsp;Jiao Li ,&nbsp;Yaming Cao ,&nbsp;Lunhao Bai ,&nbsp;Jinghan Lu","doi":"10.1016/j.ijpddr.2024.100563","DOIUrl":"10.1016/j.ijpddr.2024.100563","url":null,"abstract":"<div><h3>Background</h3><p>Studying and discovering the molecular mechanism of <em>Plasmodium</em> sexual development is crucial for the development of transmission blocking drugs and malaria eradication. The aim of this study was to investigate the feasibility of using phosphatase inhibitors as a tool for screening proteins essential for <em>Plasmodium</em> sexual development and to discover proteins affecting the sexual development of malaria parasites.</p></div><div><h3>Methods</h3><p>Differences in protein phosphorylation among <em>Plasmodium</em> gametocytes incubated with BVT-948 under <em>in vitro</em> ookinete culture conditions were evaluated using phosphoproteomic methods. Gene Ontology (GO) analysis was performed to predict the mechanism by which BVT-948 affected gametocyte–ookinete conversion. The functions of 8 putative proteins involved in <em>Plasmodium berghei</em> sexual development were evaluated. Bioinformatic analysis was used to evaluate the possible mechanism of PBANKA_0100800 in gametogenesis and subsequent sexual development.</p></div><div><h3>Results</h3><p>The phosphorylation levels of 265 proteins decreased while those of 67 increased after treatment with BVT-948. Seven of the 8 genes selected for phenotype screening play roles in <em>P. berghei</em> sexual development, and 4 of these were associated with gametocytogenesis. PBANKA_0100800 plays essential roles in gametocyte–ookinete conversion and transmission to mosquitoes.</p></div><div><h3>Conclusions</h3><p>Seven proteins identified by screening affect <em>P. berghei</em> sexual development, suggesting that phosphatase inhibitors can be used for functional protein screening.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100563"},"PeriodicalIF":4.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000447/pdfft?md5=9f49542e884503e417896ae68e574d58&pid=1-s2.0-S2211320724000447-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Giardia duodenalis by isocryptolepine -triazole adducts and derivatives","authors":"Supaluk Popruk ,&nbsp;Jumreang Tummatorn ,&nbsp;Suthasinee Sreesai ,&nbsp;Sumate Ampawong ,&nbsp;Tipparat Thiangtrongjit ,&nbsp;Phornpimon Tipthara ,&nbsp;Joel Tarning ,&nbsp;Charnsak Thongsornkleeb ,&nbsp;Somsak Ruchirawat ,&nbsp;Onrapak Reamtong","doi":"10.1016/j.ijpddr.2024.100561","DOIUrl":"10.1016/j.ijpddr.2024.100561","url":null,"abstract":"<div><p><em>Giardia duodenalis</em>, a widespread parasitic flagellate protozoan causing giardiasis, affects millions annually, particularly impacting children and travellers. With no effective vaccine available, treatment primarily relies on the oral administration of drugs targeting trophozoites in the small intestine. However, existing medications pose challenges due to side effects and drug resistance, necessitating the exploration of novel therapeutic options. Isocryptolepine, derived from <em>Cryptolepis sanguinolenta</em>, has demonstrated promising antimicrobial and anticancer properties. This study evaluated eighteen isocryptolepine-triazole adducts for their antigiardial activities and cytotoxicity, with ISO2 demonstrating potent antigiardial activity and minimal cytotoxicity on human intestinal cells. Metabolomics analysis revealed significant alterations in <em>G. duodenalis</em> metabolism upon ISO2 treatment, particularly affecting phospholipid metabolism. Notably, the upregulation of phytosphingosine and triglycerides, and downregulation of certain fatty acids, suggest a profound impact on membrane composition and integrity, potentially contributing to the parasite's demise. Pathway analysis highlighted glycerophospholipid metabolism, cytochrome <em>b</em>5 family heme/steroid binding domain, and P-type ATPase mechanisms as critical pathways affected by ISO2 treatment, underscoring its importance as a potential target for antigiardial therapy. These findings shed light on the mode of action of ISO2 against <em>G. duodenalis</em> and provide valuable insights for further drug development. Moreover, the study also offers a promising avenue for the exploration of isocryptolepine derivatives as novel therapeutic agents for giardiasis, addressing the urgent need for more effective and safer treatment options.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100561"},"PeriodicalIF":4.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000423/pdfft?md5=cf1b4f8e64b6cac6a25597bf8c18ea7c&pid=1-s2.0-S2211320724000423-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Efficacy of flukicides against Fasciola hepatica and first report of triclabendazole resistance on German sheep farms\" [Int. J. Parasitol. Drugs Drug Resist. 23 (2023) 94-105].","authors":"Alexandra Kahl, Georg von Samson-Himmelstjerna, Christina Helm, Jane Hodgkinson, Diana Williams, Wiebke Weiher, Werner Terhalle, Stephan Steuber, Martin Ganter, Jürgen Krücken","doi":"10.1016/j.ijpddr.2024.100562","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2024.100562","url":null,"abstract":"","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":" ","pages":"100562"},"PeriodicalIF":4.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}